ABSTRACT Hypothesis: We hypothesize the diffusion properties and microstructure change across the entire length of the spinal cord during recovery from SCI. Also, we postulate that diffusion measurements and tissue sparing can be used to estimate sensorimotor function. In addition, we hypothesize that DTI is sensitive to regenerative interventions. Preliminary Data: Pilot studies have demonstrated the feasibility of obtaining DTI images of the injured and non-injured rat spinal cord using a high field (9.4T) small animal magnet. DTI images appear to follow expected patterns predicted by images obtained in chronic human SCI, with changes in diffusivity both at the injury site and in regions distant from the injury. Of particular note, reductions in diffusion appear in regions o fthe spinal cord distant from the injury site that correlate with histological data indicating cellular responses in neurons ofthe corresponding gray matter. Further, pilot data indicate that diffusion patterns are related to functional connectivity of the spinal cord, evidenced by correlations with spinal somatosensory evoked potentials (SSEPs). In separate studies, we have also demonstrated specific structural changes in the cervical dorsal hom of the rat spinal cord subjected to thoracic contusion injury and treated with stem cell grafts. These structural changes correlated with increased proliferation of pain fibers, which functionally resulted in the development of forelimb allodynia. We propose using this treatment paradigm, with well documented structural and functional changes, to test the diagnostic and prognostic abilities of DTI. Research Objectives: The overall goal of this project is to determine whether DTI can provide a non invasive imaging correlate of spinal cord structure and function following injury and regenerative therapies in a rat model of SCI. We plan to pursue this goal through three specific objectives. (1) Characterize region-specific changes in diffusivity during recovery from SCI. (2) Characterize functional correlates to DTI in the spinal cord during recovery from SCI. (3) Determine the sensitivity ofDTI to neuronal stem cell treatments following SCI. Our approach will use in vivo and ex vivo OTI to detemi.ine histological correlates during recovery from SCI. We will then determine the behavioral and electrophysiological functional correlates to DTI to histology and axonal morphometry. Lastly, we will determine the sensitivity of DTI to regeneration interventions with known changes in structure and function. The translational nature of this project is reflected by direct future application in humans if DTI is found to be able to detect histologically verifiable changes in morphology in the injured spinal cord.